Cardiac Myosin-Binding Protein C in Suspected Acute Coronary Syndrome: From Sarcomeric Injury Biology to Decision-Grade Risk Stratification

Figure 4. From biomarker to decision-grade evidence: an implementation framework for cMyC. Note: The clinical adoption of cMyC requires a staged evidentiary pathway extending beyond analytical detectability or diagnostic association. First, assays must demonstrate analytical validity, including precision, epitope and fragment standardization, analytical robustness and inter-assay consistency. Second, clinical validity must be established across multicenter populations and relevant phenotypes, including early presenters and patients with CKD, HF or multimorbidity. Third, cMyC must demonstrate incremental value over contemporary hs-cTnT and hs-cTnI clinical decision pathways, particularly through observe-zone reduction, earlier triage or phenotype-specific advantage. Fourth, biomarker results must change clinical decisions, including rule-in/rule-out allocation, emergency department length of stay, resource use or clinician decision support. Fifth, any accelerated pathway must preserve safety, including missed MI and 30-day MACE outcomes. Sixth, implementation must be economically justified. Finally, guideline adoption requires feasibility, clinician adherence and integration into validated…

Figure 1. Molecular-to-clinical framework integrating the determinants of circulating cMyC with relevant clinical decisions. Note: The domain architecture is retained after dephosphorylation, whereas proteolytic fragmentation is shown as a separate subsequent process. The key message is that cMyC concentration is shaped by sarcomeric origin, ischemia–reperfusion processing, assay epitope recognition and patient phenotype; it should therefore be interpreted as decision-support information rather than as a stand-alone diagnostic label. The sarcomeric architecture and regulatory biology are supported by references [16,17,18,19]; ischemia–reperfusion-related processing and release kinetics by [7,8,9,16]; assay epitope and fragment recognition by [9,10]; phenotype-dependent interpretation by [15,20,21,29]; and the clinical decision framework by [11,12,13,14,23]. Throughout the figure, cMyBP-C denotes the intracellular sarcomeric protein, whereas cMyC denotes the circulating biomarker signal measured by an assay; neither term refers to the MYC proto-oncogene or c-Myc protein. The pale-red compartment in panel (C) represents the circulating blood compartment and does not indicate a separate…

Figure 2. Proposed phenotype-specific use of cMyC in suspected acute coronary syndrome. Note: The potential clinical utility of cMyC depends on time from symptom onset and clinical phenotype. In very early presenters, cMyC may provide the greatest incremental value by accelerating rule-out or rule-in decisions when hs-cTn signals are still evolving. In patients presenting after 1–3 h, cMyC is more plausibly an adjunct to established 0/1 h or 0/2 h pathways. In later presenters, standard hs-cTn dynamics, clinical assessment and imaging are likely to dominate. In CKD, HF and older multimorbid patients, interpretation requires caution because chronic myocardial injury may reduce specificity. After STEMI/PCI, cMyC should be considered a potential prognostic or infarct-burden marker rather than a diagnostic tool. Recurrent chest pain after recent MI remains an attractive but insufficiently validated use case. Abbreviations: MVO, microvascular obstruction; PCI, percutaneous coronary intervention.

Figure 3. Conceptual biomarker kinetics of cMyC versus hs-cTnI and hs-cTnT after symptom onset and after reperfusion. Note: Panel (A) illustrates schematic biomarker release patterns after symptom onset in suspected ACS. cMyC may provide an earlier circulating signal during the first hours after injury, when diagnostic uncertainty is greatest and hs-cTnT and hs-cTnI concentrations or deltas may still be evolving. This potential advantage is expected to diminish as standard hs-cTn pathways become increasingly informative. Panel (B) illustrates conceptual kinetics after reperfusion in STEMI. In this setting, cMyC should not be viewed as a diagnostic marker for STEMI, but as a potential post-reperfusion phenotyping signal related to infarct burden, microvascular obstruction, and remodeling risk. The curves are schematic and were not fitted to or digitized from a single clinical cohort. Panel A is informed by reported early-release and diagnostic studies [7,8,9,11,30,31], whereas Panel B is informed by serial post-reperfusion and CMR-linked studies [32,35,36,37,38]. The figure illustrates relative temporal concepts rather than fixed concentrations, peak times, or universal diagnostic…